Formation of 3-Butenoates from Crotonyl Chloride in the Presence of Amines

As alkene metathesis has developed into one of the tools of organic synthesis, many practical questions have arisen. In the course of a synthesis (Organic Lett. 2007, 9, 1635) of the important neuropharmacological tool (-)-kainic acid 7, Tohru Fukuyama of the University of Tokyo prepared the key intermediate 1 by chiral auxiliary mediated coupling of crotonyl chloride with acetadehyde. Dibal reduction gave the hemiaminal, which underwent reductive amination with glycine methyl ester, leading to the alkene 2. Alkene metathesis of the derived ester 3 to form the unsaturated lactone 4 was then examined in detail. It was found that 0.5 mol % of the second generation Hoveyda catalyst was sufﬁcient to cyclize 3 to 4 in 92% yield. With 0.8 mol %, the yield was 99%. The key to the efﬁcacy of this cyclization was the use of 1,2-dichloroethane at reﬂux as the reaction solvent. The macrolide pladienolide D 14 induces in vivo tumor regression in several human cancer xenograft models. This activity was important enough that a team at Esai Co., Ltd in Tsukuba headed by Yoshihiko Kotake undertook the total synthesis (Angew. Chem. Int. Ed. 2007, 46, 4350). Their approach used two alkene metathesis steps. To prepare the substrate for the macrolide construction, the alcohol 8 and the acid 9, each prepared by chiral auxiliary control, were coupled to give the ester 10. An extensive investigation led to alkene metathesis conditions that were satisfactory, the use of the second generation Hoveyda catalyst in refluxing toluene. A significant competing side reaction was the migration of the monosubstituted alkene of 10 to make the alkenyl ether. The second alkene metathesis step was the coupling of 12 with 13. The most effective catalyst in this case was the second generation Grubbs. Note that the free alcohol 13 participated successfully in the cross-coupling. According to the authors, this is one of just a few examples of successful cross coupling of an alkene adjacent to a quaternary center. The stereocontrolled construction of trisubstituted alkenes by metathesis is a particular challenge.

Download Full-text

ChemInform Abstract: LOW RESOLUTION SPECTRA AND CONFORMATIONS OF CROTONYL CHLORIDE AND CROTYL ALCOHOL

Chemischer Informationsdienst ◽

10.1002/chin.197906047 ◽

1979 ◽

Vol 10 (6) ◽

Author(s):

D. K. LUM ◽

L. E. BAUMAN ◽

T. B. JUN. MALLOY ◽

R. L. COOK

Keyword(s):

Low Resolution ◽

Crotyl Alcohol ◽

Crotonyl Chloride

Download Full-text

Low resolution spectra and conformations of crotonyl chloride and crotyl alcohol

Journal of Molecular Structure ◽

10.1016/0022-2860(78)87092-6 ◽

1978 ◽

Vol 50 (1) ◽

pp. 1-6 ◽

Cited By ~ 9

Author(s):

D.K. Lum ◽

L.E. Bauman ◽

Thomas B. Malloy ◽

Robert L. Cook

Keyword(s):

Low Resolution ◽

Crotyl Alcohol ◽

Crotonyl Chloride

Download Full-text

Spectroscopic studies on crotonyl chloride and dimethyl acryl chloride

Spectrochimica Acta Part A Molecular Spectroscopy ◽

10.1016/0584-8539(89)80012-1 ◽

1989 ◽

Vol 45 (5) ◽

pp. 595-602 ◽

Cited By ~ 5

Author(s):

R.K. Gupta ◽

R. Prasad ◽

Hari L. Bhatnagar

Keyword(s):

Spectroscopic Studies ◽

Crotonyl Chloride

Download Full-text

Acylation of Some Thiophenes with Crotonyl Chloride

Journal of the American Chemical Society ◽

10.1021/ja01178a504 ◽

1949 ◽

Vol 71 (10) ◽

pp. 3542-3543

Author(s):

Charles K. Bradsher ◽

Frances C. Brown ◽

R. J. Grantham

Keyword(s):

Crotonyl Chloride

Download Full-text

N-(2-Diazo-3-oxoalkanoyl)glycine esters. I. Synthesis of 4- and 5-phenoxyl derivatives and isomerization of N-(2-diazo-3-oxo-3-phenylpropanoyl)glycine ethyl ester

Canadian Journal of Chemistry ◽

10.1139/v67-281 ◽

1967 ◽

Vol 45 (15) ◽

pp. 1727-1734 ◽

Cited By ~ 11

Author(s):

James H. Looker ◽

James W. Carpenter

Keyword(s):

Ethyl Ester ◽

Ethyl Esters ◽

Chromatographic Purification ◽

Dimroth Rearrangement ◽

Chromatographic Procedure ◽

Propionyl Chloride ◽

Glycine Ethyl Ester ◽

Crotonyl Chloride ◽

Weight Data ◽

Pyrazoline Derivative

A new preparative procedure for N-(diazoacetyl)glycine ethyl ester is described. The interaction of N-(diazoacetyl)glycine ethyl ester with four phenoxyacetyl chlorides gives the 4-phenoxylderivatives of N-(2-diazo-3-oxobutanoyl)glycine ethyl ester, and with β-(o-methoxyphenoxy)-propionyl chloride yields N-[2-diazo-3-oxo-5-(o-methoxyphenoxy)pentanoyl]glycine ethyl ester. A general chromatographic procedure for separating N-(2-diazo-3-oxoalkanoyl)glycine ethyl esters from N-(chloroacetyl)glycine ethyl ester has been developed. Crotonyl chloride reacts with a 1 mole excess of N-(diazoacetyl)glycine ethyl ester to form N-(2-diazo-3-oxo-4-hexenoyl)glycine ethyl ester, and with a 2 mole excess to form N-{2-diazo-3-oxo-3-[4′-methyl-5′(carboethoxymethyl)carbamoyl-Δ2pyrazolin-3′-yl]propanoyl}glycine ethyl ester, presumably by isomerization of an initially formed Δ1-pyrazoline derivative. The interaction of benzoyl and m-bromobenzoyl bromide with N-(diazoacetyl)glycine ethyl ester results initially in yellow oily products which, on the basis of spectral data, are the expected N-(2-diazo-3-oxo-3-rylpropanoyl)glycine ethyl esters. During chromatographic purification and (or) attempted crystallization, there occurs an isomerization to colorless crystalline products. The analytical and molecular weight data, together with the spectral evidence, support the tentative assignment of 1,2,3-triazole structures to the isomerization products. A spontaneous reverse Dimroth rearrangement is postulated.

Download Full-text

2,2-Dimethylsuccinic acid derivatives in isoprenoid synthesis: a 2,2-dimethylvinyl anion equivalent in the synthesis of ar-atlantone, ar-turmerone, and prenylated aromatic compounds

Canadian Journal of Chemistry ◽

10.1139/v92-169 ◽

1992 ◽

Vol 70 (5) ◽

pp. 1317-1322 ◽

Cited By ~ 5

Author(s):

George M. Strunz ◽

Li Ya

Keyword(s):

Aromatic Compounds ◽

Dicarboxylic Acids ◽

Lead Tetraacetate ◽

Keto Acid ◽

Acid Catalyzed ◽

Crotonyl Chloride ◽

Hydrolysis Of

The anion of methyl 2,2-dimethylsuccinate was alkylated with benzylic bromides to give the corresponding 3-substituted-2,2-dimethylsuccinates. Hydrolysis to the dicarboxylic acids, followed by bisdecarboxylation with lead tetraacetate, afforded 1-aryl-3-methyl-2-butenes, which are model prenylated aromatic compounds. Acylation of methyl 2,2-dimethylsuccinate with E-3-(4′-methylphenyl) crotonyl chloride gave the substituted succinate 9. Hydrolysis of the ester groups and acid-catalyzed decarboxylation of the resulting β-ketoacid produced the keto acid 10, which was decarboxylated by the Kochi method, furnishing ar-atlantone. Hydrogenation of 10 yielded 12, which on similar decarboxylation afforded ar-turmerone.

Download Full-text

Preparation of cis-crotonyl chloride

Canadian Journal of Chemistry ◽

10.1139/v68-075 ◽

1968 ◽

Vol 46 (3) ◽

pp. 466-468 ◽

Cited By ~ 8

Author(s):

M. B. Hocking

Keyword(s):

Trans Isomer ◽

Acid Chloride ◽

Boiling Point ◽

Free Acid ◽

Isomer Separation ◽

Crotonyl Chloride ◽

Chloride Contaminated

Published methods for the preparation of cis-crotonyl chloride were found to give a product contaminated with appreciable proportions of the trans isomer. Separation of these two isomers was found to be impossible because of the small boiling point difference and the readiness with which the cis acid chloride isomerizes to the trans. Herein are outlined the precautions necessary to obtain pure cis-crotonyl chloride contaminated only with the free acid, from which it is readily separated by cold distillation.

Download Full-text